Long-term calorie restriction decreases metabolic cost of movement and prevents decrease of physical activity during aging in rhesus monkeys
Introduction
The concept of delaying the morbidities of aging through caloric restriction (CR) can be traced back at least three centuries to, Kaibara Ekiken (1630–1714) who wrote at the age of 83 years in his Yōjōkun (The Book of Life-nourishing Principles) that one way to remain healthy and increase longevity is to stop eating when the stomach is less than full (Kaibara and Translated by Wilson, 2009 (originally written in 1712)). Far more recently, careful laboratory studies of CR without malnutrition have shown that CR does indeed extend the maximal life span in multiple short-lived species (Anderson et al., 2009). In nonhuman primates, CR has been shown to reduce or delay the onset of diverse age-related diseases and disorders such as diabetes (Gresl et al., 2001), sarcopenia (Colman et al., 2008), immune senescence (Messaoudi et al., 2006), hypertension, cancer, bone demineralization, and brain atrophy (Colman and Anderson, 2011, Colman et al., 2009). The study of rhesus monkeys at the University of Wisconsin, begun in 1989, also demonstrated a reduction in age-related mortality in CR animals (Colman and Anderson, 2011, Colman et al., 2009), although an effect on longevity was not found in a second study performed at the National Institute of Aging (Mattison et al., 2012).
In rhesus monkeys CR is associated with an initial weight loss, but body weight plateaus indicating that caloric balance is reestablished during the CR intervention (Colman et al., 2008). The metabolic transition is characterized by a decrease in energy expenditure (Ramsey et al., 2000a), presumably to match the reduction in energy intake. Randomized controlled trials for CR have shown that much of the adaptation is driven by a reduction in body size, but reductions in energy expenditure that cannot be explained simply by the smaller body size have been reported (DeLany et al., 1999, Ramsey et al., 1997, Weed et al., 1997), although findings are inconsistent (Kemnitz et al., 1993, Moscrip et al., 2000, Ramsey et al., 1997, Weed et al., 1997).
Daily energy expenditure has three major components: resting metabolic rate, the thermic effect of food, and the energy expenditure of physical activity. Most studies to date have focused on resting metabolic rate and total energy expenditure. Physical activity has also been studied and earlier reviews of the subject concluded that CR did not alter physical activity in macaques (Heilbronn and Ravussin, 2003, Ingram et al., 2001, Roth et al., 2002). In rodent studies, however, differing results have been reported; specifically, it has been found that wheel-running activity of rats was generally reduced in CR groups early in life, but CR resulted in higher activity levels later in life when control groups began to exhibit a marked age related decline in activity (Goodrick et al., 1983).
The objective of this current study was to determine the metabolic and behavioral adaptations to long-term diet restriction in rhesus monkeys. Longitudinal changes in energy expenditure including the metabolic cost of movement, and duration and intensity of physical activity during 24 h were determined in monkeys enrolled in the on-going University of Wisconsin CR and Aging study (Kemnitz et al., 1993, Ramsey et al., 2000a). The youngest animals in this longitudinal study were 19 years of age at the last assessment time-point for this analysis, an age considered past the age of sarcopenia onset, which has been clinically assessed to be 14–16 years of age in rhesus monkeys at the Wisconsin National Primate Research Center (WNPRC) (Colman et al., 2005).
Section snippets
Animals
The CR study at WNPRC has been previously described (Kemnitz et al., 1993, Ramsey et al., 1997). Briefly, the study includes three groups of adult rhesus monkeys (Macaca mulatta of Indian derivation); 30 male monkeys entered in the study in 1989 (Group 1), and 30 females (Group 2) and an additional 16 males (Group 3) were introduced in 1994. All groups averaged ~ 10 years of age at the onset of CR. Within each group animals were stratified by body weight and randomly assigned to either the
Dietary intake
The impact of age on calorie intake has influenced the extent of CR achieved in this study over time. Until 2001 the difference in energy intake between C and CR had been about 28–30% (Blanc et al., 2003); however, the difference in energy intake between C and CR decreased thereafter. As the study progressed, the 18 C animals ate 11% less than at the outset of the study (2.72 MJ/d at 1999 to 2.41 MJ/d at 2007, P = 0.020 by paired t-test). Energy intake did not change over the same period for the 24
Discussion
The present study provides the most comprehensive analysis of energy expenditure in nonhuman primates under control and CR conditions conducted to date. To circumvent the prior limitation of possible night-time wakefulness, we refined our proxy resting metabolic rate measurement by using a sleeping metabolic rate (lowest 3 h night time energy expenditure) in place of a 12 h night-time metabolic rate, and confirmed our previous report of reduced resting metabolic rate among CR animals (Blanc et
Conclusion
Short-term (< 1 yr) calorie restriction (CR) lowers TEE, activity energy expenditure, and physical activity in human and non-human primates. In long-term CR, however, CR does not decrease either TEEDLW or 24 h EEchamber even though SMR is lower in CR non-human primates. Furthermore, CR animals maintain a higher physical activity level than C animals, with significantly longer duration of physical activity and more frequent high intensity activities observed in CR animals. Importantly, the metabolic
Conflict of interest
The authors have no conflicts of interests.
Acknowledgment
This work was supported by grants P01 AG-11915 (to R. Weindruch) and P51 RR000167 (to the Wisconsin National Primate Research Center, University of Wisconsin, Madison). This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01.
References (50)
- et al.
Metabolic reprogramming, caloric restriction and aging
Trends Endocrinol. Metab.
(2010) - et al.
Energy requirements in the eighth decade of life
Am. J. Clin. Nutr.
(2004) - et al.
Muscle mass loss in rhesus monkeys: age of onset
Exp. Gerontol.
(2005) - et al.
Calorie restriction and aging: review of the literature and implications for studies in humans
Am. J. Clin. Nutr.
(2003) - et al.
Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys
Exp. Gerontol.
(2012) - et al.
Metabolizable energy intake during long-term calorie restriction in rhesus monkeys
Exp. Gerontol.
(2007) - et al.
Dietary restriction and aging in rhesus monkeys: the University of Wisconsin study
Exp. Gerontol.
(2000) - et al.
Metabolic shifts due to long-term caloric restriction revealed in nonhuman primates
Exp. Gerontol.
(2009) - et al.
Activity measures in rhesus monkeys on long-term calorie restriction
Physiol. Behav.
(1997) Physical activity as determinant of daily energy expenditure
Physiol. Behav.
(2008)
Melatonin promotes sleep in three species of diurnal nonhuman primates
Physiol. Behav.
Caloric restriction and aging: studies in mice and monkeys
Toxicol. Pathol.
Energy expenditure of rhesus monkeys subjected to 11 years of dietary restriction
J. Clin. Endocrinol. Metab.
Assessment of nutritional status in rhesus monkeys: comparison of dual-energy X-ray absorptiometry and stable isotope dilution
J. Med. Primatol.
Assessment of energy-expenditure for physical-activity using a triaxial accelerometer
Med. Sci. Sports Exerc.
Nonhuman primate calorie restriction
Antioxid. Redox Signal.
Attenuation of sarcopenia by dietary restriction in rhesus monkeys
J. Gerontol. A Biol. Sci. Med. Sci.
Caloric restriction delays disease onset and mortality in rhesus monkeys
Science
The effect of lateral stabilization on walking in young and old adults
IEEE Trans. Biomed. Eng.
Long-term calorie restriction reduces energy expenditure in aging monkeys
J. Gerontol. A Biol. Sci. Med. Sci.
Effects of intermittent feeding upon growth, activity, and lifespan in rats allowed voluntary exercise
Exp. Aging Res.
Dietary restriction and glucose regulation in aging rhesus monkeys: a follow-up report at 8.5 yr
Am. J. Physiol. Endocrinol. Metab.
Nonexercise movement in elderly compared with young people
Am. J. Physiol. Endocrinol. Metab.
Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial
JAMA
Aging and caloric restriction in nonhuman primates: behavioral and in vivo brain imaging studies
Ann. N. Y. Acad. Sci.
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